Dr. Bailey-Wilson is collaborating with Drs. Barbara and Ronald Klein on analyses of existing family data from the Beaver Dam Eye Study. A private census of the town and township of Beaver Dam, Wisconsin was performed and all individuals between the ages of 43-84 were asked to enroll, given extensive eye examinations and asked to fill out a questionnaire that measures environmental risk factor exposures. We have previously analyzed STRP genome-wide scan (GWS) data on the entire Beaver Dam cohort of families for glaucoma, IOP, refractive error, myopia, hyperopia, and various forms of cataracts. We published a letter to the editor that highlights a possible combined glaucoma/high IOP risk locus, and an article on macular degeneration. Linkage analyses using a new SNP linkage panel with multiple traits including: refraction, myopia, nuclear sclerosis, etc are underway. Dense SNPs for finemapping of Chromosome 19 for IOP and 2 smaller glaucoma-associated regions on chromosomes 5 and 6 are currently being genotyped and will be analyzed in the next fiscal year.[unreadable] [unreadable] A study of the genetics of myopia with Dr. Dwight Stambolian is ongoing. Dr. Stambolian has collected pedigrees with myopia from 4 populations. Analyses of refractive error in the Ashkenazi Jewish and Amish families have revealed evidence of a QTL on chromosome 1. A set of about 1500 SNPs were genotyped in our Ashkenazi and Amish families to follow up the linkage of refractive error on chromosome 1; these data analyses are ongoing. New families have been genotyped for a genome wide scan and a paper presenting confirmation of our previous chromosome 22 linkage results for myopia in these new Ashkenazi families has been published previously. Two papers describing our myopia and refractive error linkage results in a set of African-American families and a set of Caucasian families were published or are in press and a metaanalysis of results from all of the populations is ongoing. We found significant evidence of linkage of refractive error to chromosome 7q in the African-American pedigrees and are planning to genotype a finemapping panel of SNPs to follow-up this region. Finemapping in one of our previously published linkage regions on chromosome 22 for myopia has resulted in significant evidence of association and we are following this up by sequencing 3 candidate genes in the associated region.[unreadable] [unreadable] Dr. Bailey-Wilson and several members of her group have received permission to analyze genetic data from the Framingham Eye Study and Offspring Study cohorts. The sample consists of about 1100 nuclear families whose members have been phenotyped extensively and genotyped for 116,000 SNPs and 600 microsatellite marker loci. Genomewide linkage and association analyses of traits related to myopia and hyperopia, refractive error and glaucoma related traits (IOP, Cup-to Disc, Glaucoma) are ongoing.[unreadable] [unreadable] Drs. Wojciechowski and Bailey-Wilson have started a new collaboration with Drs. Chris Murphy, Donald Mutti and Edwin Stone on a study of myopia in English springer spaniel dogs, a model organism for human myopia. Dr. Stones laboratory will perform genotyping using a recently developed SNP chip for dogs, and we will perform the analyses.[unreadable] [unreadable] Dr. Bailey-Wilson is a member of a collaborative study of Attention Deficit Hyperactivity Disorder, collaborating with Drs. Max Muenke and Dr. Mauricio Arcos-Burgos of NHGRI and University of Antioquia, Columbia. Dr. Bailey-Wilson's role is to help with study design and to serve as advising statistical geneticist on the project. Genome-wide scan genotyping and linkage analysis has been completed on the first set of families followed by finemapping. We have previously shown evidence of linkage of ADHD to 4q132, 5q333, 11q22, and 17p11. Association studies have been performed to follow up our linkage results, and significant associations have been replicated in additional samples. Papers are in preparation.[unreadable] [unreadable] Dr. Bailey-Wilson is collaborating with Dr. Hasan Albacha-Hejazi of the Syrian Arab Republic, Dr. Diego Wyszynski of Boston University and Dr. Terri Beaty of Johns Hopkins School of Public Health on a linkage study of oral clefts. Data collection is ongoing in the Syrian Arab Republic and more genotyping will be performed when enrollment of a total of 50 families informative for linkage is completed. [unreadable] [unreadable] Dr. Bailey-Wilson is working with Drs. Forbes Porter of NIH and Elaine Tierney of Kennedy Krieger on a genetic study of autism. Evidence for linkage of autistic individuals with hypocholesterolemia has been found. Confirmation in additional data is underway and additional family data is being collected.[unreadable] [unreadable] Dr. Bailey-Wilson also serves in an advisory role on study design and interpretation of results for the Familial Intracranial Aneurysm consortium. This consortium is using both linkage and genome-wide association methods to detect genetic predisposition to this type of familial strokes. Results of a genome-wide linkage study were published this year.[unreadable] [unreadable] Another set of projects led by Dr. Priya Duggal, a senior postdoctoral trainee in the Section, encompass the human genetic predisposition to infectious diseases including Visceral leishmaniasis, Amebiasis and HIV/AIDS.[unreadable] [unreadable] Dr. Duggal collaborates with Dr. Mary Wilson of the University of Iowa and [unreadable] Dr. Selma Jeronimo of Natal, Brazil on the study of Visceral leishmaniasis (VL).[unreadable] VL is a potentially fatal disease caused by the protozoan Leishmania chagasi that is carried by the sandfly. We have completed a genome wide linkage scan for the DTH immune response, and a paper reporting the results has been published this year. We are currently choosing finemapping the regions in and around our linkage peaks. [unreadable] [unreadable] Dr. Duggal collaborates with Dr. William Petri of the University of Virginia and Dr. Rashidul Haque at the ICDDR,B, Dhaka, Bangladesh on the host susceptibility to Amebiasis. Amebiasis is a large contributor to diarrheal disease in the developing world, and is caused by infection of the intestine by the parasite Entamoeba histolytica. This year we published a paper that identified an association with HLA class II alleles and cryptosporidium, another cause of diarrheal disease in these children and another concerning susceptibility to infection. We have genotyped tagging SNPs in 90 candidate genes for 450 children in this study. Of the 20 genes already analyzed, we have identified a strong association with a functional coding SNP in the Leptin Receptor gene.